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Background  Proprotein convertase subtilisin kexin 9 ( PCSK 9) inhibitors reduce low‐density lipoprotein cholesterol ( LDL ‐C) and improve outcomes in the general population.  HIV ‐infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus ( HCV ) coinfection, making  PCSK 9 inhibition a potentially attractive therapy.    Methods and Results  We studied 567 participants from a clinic‐based cohort to compare  PCSK 9 levels in patients with  HIV / HCV  coinfection (n=110) with those with  HIV  infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median  LDL ‐C level was 100 mg/dL ( IQR  77–124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol,  LDL ‐C, and high‐density lipoprotein cholesterol levels were lower in coinfected patients compared with controls ( P <0.001).  PCSK 9 was 21% higher in  HIV / HCV ‐coinfected patients versus controls (95%  CI  9–34%,  P <0.001) and 11% higher in coinfected individuals versus those with  HIV  infection alone (95%  CI  3–20%,  P =0.008). After adjustment for cardiovascular risk factors,  HIV / HCV  coinfection remained significantly associated with 20% higher  PCSK 9 levels versus controls (95%  CI  8–33%,  P =0.001). Interleukin‐6 levels increased in a stepwise fashion from controls (lowest) to  HIV ‐infected to  HIV / HCV ‐coinfected individuals (highest) and correlated with  PCSK 9 ( r =0.11,  P =0.018).    Conclusions  Despite having  lower   LDL ‐C, circulating  PCSK 9 levels were  increased  in patients coinfected with  HIV  and  HCV  in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin‐6. Clinical trials should be conducted to determine the efficacy of targeted  PCSK 9 inhibition in the setting of  HIV / HCV  coinfection.

journal of the american heart association

HIV  and Hepatitis C–Coinfected Patients Have Lower Low‐Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 ( PCSK 9): An Apparent “ PCSK 9–Lipid Paradox”